Process for the preparation of substituted guanidines



Patented Nov. 8, 1-927,

- UNITED STATES PATENT OFFICE.

EMIL KIJINE, F HUDSON, NEW YORK, ASSIGNOR, BY MESNE ASSIGNMENTS, TO TH]! GRASSELLI CHEMICAL COMPANY, OF CLEVELAND, OHIO, A CORPORATION OI OHIO.

PROCESS FOR THE PREPARATION OF SUBSTITUTED GUANIDINES.

Ho 1] swing.

This invention relates to a process for the preparation of substituted guanidines.

Diphenylguanidine has been prepared (see Hofi'man, Ben, 2, 460) by desulfurizing 5 thio carbanilide with lead oxid in a solution of alcoholic ammonia at or near the boiling point of the solution. In United States Patent No. 1,446,818 there is described a method for the production of J0 diarylguanidines, particularly diphenylguanidine, by subjecting alcoholic ammoniacal solutions of diarylthioureas, specifically thio carbanilide, to the action of lead oxid at a temperature not greater than 60 C. In

United States Patent No. 1,437,419 there is described a similar method, using lead oxid as the desulturizing agent, for the preparation of trisubstituted guanidines, specifically the tri toluyl guanidine.

Alway and Vail glsee Am. Chem. J. 28, 158,-l90 l) have s own by their work on the preparation of aromatic guanidines other than diphenylguanidine that freshly precipitated lead hydroxide ,in the form of a thin paste in alcohol is a better desulfurizing agent than lead oxid. The use of freshly precipitated lead hydroxid as the desulfurizing agent, however, is not well adapted to commercial operation due to the difliculty and inconvenience involved in the maintenance of a supply thereof. i

I have now found'that substituted guanidines can be produced by desulfurizing substituted thio-ureas in solution by the use instead of lead oxid or hydroxid as in the prior processes referred to, of a substantially water-soluble salt of a heavy metal such as lead nitrate, chloride acetate, eto., ferric sulfate, copper chloride, etc. which salts liberate a metallic oxid or h droxid capable of accomplishing the desul urination in an alkaline medium and in presence 5 of ammonia or an amine, such as aniline, toluidine, xylidine, etc.; i"or convenience, am-

nionia and the amines will be referred to hereinafter as nitrogenous bases.

By the use of the expression a substantially water-soluble salt of a heavy metal and the expression a substantially watersoluble lead salt I intend, for the purposes of the present invention, to exclude those salts of heavy metals and lead salts respectively which have a water solubility less Application filed October 8, 1924. Serial No. 742,070.

than about 0.5 part per 100 parts of cold water.

The process is particularly designed for the production of diphenylguanidine and will be illustrated in the following example 1n connection therewith, it being understood however that the invention is not limited to the specific materials and proportions thereof and details of procedure and conditions described:

Ewample.

228 pounds of thiocarbanilid, 800 pounds (130 gallons) of 60% by weight denatured alcohol and 157.2 pounds of aqua ammonia (2&2992; Nl-l are placed in a suitable kettle equipped with an agitator and a condenser. lhe temperature of the mixture is gradually raised to about 45 C. in about 15 minutes and then 380 pounds of finely powdered lead nitrate gradually added over a period of one to one and one-half hours, the temperature being held at 45 C. After all of the lead nitrate has been-added, the temperature is gradually raised in the course of 30 to 45 minutes to 70-75 C. and held at this temperature for one to one and onehalf hours or until the desulfurization is complete. out the treatment, The diphenylguanidine is then recovered from the reaction mixture for instance as follows: The mixture is filtered and the solid residue consisting principally of lead sulfid is washed first with 60% alcohol at -60 C. and then with cold water. The combined filtrate and washings is diluted with water and heated to boiling temperature and stirred for 1-2 hours. This dissolves the diphenylguanidine nitrate and leaves the gummy carbodiphenylimide formed as a by-product of the reaction and impurities undissolved. The solution is then filtered and treated with an excess of 30% caustic soda solution with stirring until the precipitation of the diphenylguanidine is-complete. The diphenylguanidine is then separated by filtration, washed with water and dried at about C.

The lead nitrate and the alcohol used in the process may be recovered for re-use in the process in any suitable manner as will be obvious to one skilled in this art.

The specific procedure described in the The mixture is agitated through foregoing example may be considerably varied. The lead nitrate may be supplied either as a. finely dii'ided solid as described or in the form" a solution and may be sub stituted by any salt, which forms a hydroxid in the presence 01 un'nnonia having a sufficient alin'nity for" suliur to accomplish the desuliurizution. The temperatures and times of treatment as well as the concentra tions of the solutions involved may be varied. It is noted however, that the temperatures which may be employed are relatively low, that the desullu'rization takes place rapidly and more completely in less time thhn when lead oxid is used as the dcsulturizingagent, that less lead and less alcohol are required, and that good yields are obtained, the prodnot being free from resinous or tar-lilre impurities. 1n the example ammonia is 12% in excess of the quantity required to react with all of the lead nitrate. T his quantity may be incre sed. The quantity of lead hi trute also may be varied. A quantity in excess of that theoretically required to as 'coniplish the rlesulfurization gives satisfactory results Diphenylguanidine prepared in accordance with the example is completely soluble in dilute hydrochloric acid solution and melts at 145-147 C.

For the preparation of other diarylguanidines the thiocarbanilide of the foregoing example is replaced by other disubstituted thioureas and for the preparation of the tri aryl guanidines the ammonia of the example is replaced by the corresponding aryl amine such as aniline, toludin, etc. Or in other Words, my invention consists generally in substituting a metallic salt for the metallic oxici used as the desulfurizing agent in prior processes for the preparation di and tri aryl guunidines such as time referred to,

I clnimzl. in pron "1 for the preparation of sub slitutcd gunniili es involying the nddi ion. oi a desuliurining agent to an alcoholic aniinonincul solution Ofrll substituted thiouree and heating; the resulting mixture, the use us desull urizing agent of a, substantially u'z-it-ci'-soliihle lead suit ln processes for the preparation of sub stituted guanidines involving the addition of u dcsullurizing agent to an alcoholic em.- inonizicul solution of e substitutes thiourea and heating the resulting mixture the use dcsult'uriziug agent of lead nitrate.

3, Process for the preparation of dierylguunidines which con'iprises addingto alcoholic uunnoniziezil solution. of s dierylthiourcu a substantially Water-soluble lead salt and heating the resulting mixture 4. Proeess tor the preparation dierylguanidines which comprises adding lead nitrate to an alcoholic unnn-oniuczil solution of a dizn'ylthiourea and heating the resulting mixture,

5. Process for the preparation of diohenylguaniclino which comprises adding to an, r 

